scholarly journals Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA

Author(s):  
Elisabeth Kowenz-Leutz ◽  
Anja Schuetz ◽  
Qingbin Liu ◽  
Maria Knoblich ◽  
Udo Heinemann ◽  
...  
1998 ◽  
Vol 334 (1) ◽  
pp. 205-210 ◽  
Author(s):  
Georgios SABATAKOS ◽  
Gareth E. DAVIES ◽  
Maria GROSSE ◽  
Anthony CRYER ◽  
Dipak P. RAMJI

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the activation of gene expression in the mammary gland during lactation. We have therefore investigated the detailed expression profile of the C/EBP family during lactation and involution of the mouse mammary gland. The expression of C/EBPβ and C/EBPδ mRNA was low during lactation, increased dramatically at the beginning of involution and remained constant thereafter. In contrast, C/EBPα mRNA expression was relatively high during the early stages of lactation, declined to low levels during the late stages of lactation and at the start of involution, and increased again during involution. Electrophoretic mobility-shift assays showed a close correlation between the expression of the C/EBP genes and the functional C/EBP DNA-binding activity and, additionally, demonstrated the participation of heterodimers, formed from among the three proteins, in DNA–protein interactions. The DNA-binding activity of the activator protein 1 (AP1) family of transcription factors was also induced during involution. These results therefore point to potentially important regulatory roles for both the C/EBP and the AP1 family during lactation and involution of the mammary gland.


1996 ◽  
Vol 16 (3) ◽  
pp. 1231-1240 ◽  
Author(s):  
D E Zhang ◽  
C J Hetherington ◽  
S Meyers ◽  
K L Rhoades ◽  
C J Larson ◽  
...  

Transcription factors play a key role in the development and differentiation of specific lineages from multipotential progenitors. Identification of these regulators and determining the mechanism of how they activate their target genes are important for understanding normal development of monocytes and macrophages and the pathogenesis of a common form of adult acute leukemia, in which the differentiation of monocytic cells is blocked. Our previous work has shown that the monocyte-specific expression of the macrophage colony-stimulating factor (M-CSF) receptor is regulated by three transcription factors interacting with critical regions of the M-CSF receptor promoter, including PU.1 and AML1.PU.1 is essential for myeloid cell development, while the AML1 gene is involved in several common leukemia-related chromosome translocations, although its role in hematopoiesis has not been fully identified. Along with AML1, a third factor, Mono A, interacts with a small region of the promoter which can function as a monocyte-specific enhancer when multimerized and linked to a heterologous basal promoter. Here, we demonstrate by electrophoretic mobility shift assays with monocytic nuclear extracts, COS-7 cell-transfected factors, and specific antibodies that the monocyte-enriched factor Mono A is CCAAT enhancer-binding protein (C/EBP). C/EBP has been shown previously to be an important transcription factor involved in hepatocyte and adipocyte differentiation; in hematopoietic cells, C/EBP is specifically expressed in myeloid cells. In vitro binding analysis reveals a physical interaction between C/EBP and AML1. Further transfection studies show that C/EBP and AML1 in concert with the AML1 heterodimer partner CBF beta synergistically activate M-CSF receptor by more then 60 fold. These results demonstrate that C/EBP and AML1 are important factors for regulating a critical hematopoietic growth factor receptor, the M-CSF receptor, suggesting a mechanism of how the AML1 fusion protein could contribute to acute myeloid leukemia. Furthermore, they demonstrate physical and functional interactions between AML1 and C/EBP transcription factor family members.


2001 ◽  
Vol 15 (2) ◽  
pp. 228-240 ◽  
Author(s):  
Shannon L. Wyszomierski ◽  
Jeffrey M. Rosen

Abstract β-Casein gene transcription is controlled primarily by a composite response element (CoRE) that integrates signaling from the lactogenic hormones, PRL, insulin, and hydrocortisone, in mammary epithelial cells. This CoRE contains binding sites for STAT5 (signal transducer and activator of transcription 5) and C/EBPβ (CCAAT/enhancer-binding protein-β) and several half-sites for glucocorticoid receptor (GR). To examine how interactions among these three transcription factors might regulateβ -casein gene transcription, a COS cell reconstitution system was employed. Cooperative transactivation was observed when all three factors were expressed, but unexpectedly was not seen between STAT5 and C/EBPβ in the absence of full-length, transcriptionally active GR. Cooperativity required the amino-terminal transactivation domain of C/EBPβ, and neither C/EBPα nor C/EBPδ was able to substitute for C/EBPβ when cotransfected with STAT5 and GR. Different GR determinants were needed for transcriptional cooperation between STAT5 and GR as compared with those required for all three transcription factors. These studies provide some new insights into the mechanisms responsible for high level, tissue-specific expression conferred by theβ -casein CoRE.


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